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The temperature was dropping that December night as I pulled the van into the Ritz Carlton in Incline Village. Sitting about 6500 ft high a couple of miles from Lake Tahoe, I shivered as I remembered the forecast – temperatures in the 20’s with snow on the way. This was not a camping night – tonight I was going to hide out in a hotel.

Weathers’ struggle for survival on Mt Everest has inspired many. His struggle pales, though, compared to what many people with ME/CFS have to endure every day.

Beck Weathers, the speaker at Simmaron Research Foundation’s Donor Appreciation night, probably would have laughed. Weather was there to talk about what his remarkable escape from 29,000 ft. Mt Everest – a gripping survival story which formed the basis for 2015 film Everest – had taught him.

Beck Weathers charged into the Ritz like a storm slamming down the slopes of Everest. It’s been over 20 years since Weathers almost lost his life during the ill-fated Everest expedition that claimed nine lives, but for Weathers, it seemed like it was yesterday as he brought each of us up onto the mountain with him.

Weathers’ wife said Weathers could talk the ears off a rubber rabbit and I believe it. The man is a natural storyteller. Those in the packed ballroom were in for a treat. I don’t know if I’ve ever heard a more evocative story.

Sound effects (wind whirling, ice crunching) were in abundance as Weathers’ voice rose and fell as he brought the fear, the exhaustion, the determination, the beauty, the failures and the triumphs of that expedition to the Simmaron Research Foundation gala dinner. It was an incredible performance.

Multiple operations formed Weathers left had into what he calls his mitt.

The scars were there, too. The missing tip of Weathers’ nose (doctors grew a new one on his forehead) and one missing and another mangled hand demonstrated the price Weathers paid for his time on the mountain.

Weathers was forty-nine at the time, an experienced amateur climber who’d summitted eight major mountains, but nothing left him prepared for what would happen on that May day in 1996. Of all the extraordinary stories to come out of that climb (read “Into Thin Air” and see “Everest“), his was the most remarkable.

Partially blind, Weathers and other climbers were caught by a sudden blizzard in the “Death Zone” above 26,000 feet on the slopes of Mount Everest. In his book, “Left for Dead”, Weathers described what happened.

“Suddenly, the blizzard detonated all around us. It crescendoed into a deafening roar. A thick wall of clouds boiled across the South Col, wrapping us in white, blotting out every discernible feature…It quickly became incredibly cold.”

As the wind suddenly rose to 70 knots and the temperatures dropped to minus 60 degrees Fahrenheit, the group struggled to survive, almost plunging off a 7,000 foot drop. A decision was made that the strongest two would try to make their way to camp. Weathers and others stayed on the Col and huddled together.

That night, a Russian climber took three more of the group down. Weathers and a Japanese climber – each in a hypothermic coma – remained. The next morning, after the storm cleared, a cardiologist determined that Weathers was too close to death to be moved: anyone caught in a hypothermic coma that high on a mountain is going to die. The cardiologist returned to camp alone.

Dead Man Walking

Late that afternoon, however, Weathers woke to see his gray, frozen, gloveless hand. Bouncing it like a block of wood off the ice somehow revived him.

Weathers hadn’t eaten for three days or had any water for two. His oxygen was long gone. By all rights, after lying in a blizzard at 26,000 feet with no sleeping bag or tent, one glove (and one hand and arm) gone, Weathers should have succumbed long ago. He’d already been pronounced and left for dead twice.

But Weathers was alive. Watching the sun begin to set, he estimated he had an hour to find camp or die. It would have been easier to slide into the cozy hypothermic coma he’d been in yesterday. Weathers could feel it tugging at him, but then something got him up and moving.

Oddly enough, it was pictures of his wife and children. Weathers had basically ditched his family in order to climb mountains. His wife was about to divorce him and his relationship with his kids – who rarely saw him – “extremely strained”. Weathers’ obsession with work, fitness and mountaineering had left little time for his family. It was as if they didn’t exist. He could disappear for weeks on an expedition – leaving them fretting – without bothering to contact them.

Yet, as he prepared himself to face a probable death, it wasn’t his work, his many awards, nor his mountain-climbing experiences that came to mind; it was the family he’d left behind.

Weathers was a pathologist with a dark secret. He’d struggled with sometimes severe depression for years. His obsessions with work, fitness and mountain climbing were in some ways simply attempts to escape his depression.

Weathers struggled up, and half-blind, picked a general direction and somehow stumbled, slid, and fell his way into camp where he was put into a tent, shoved into two sleeping bags with hot water bottles – and again pronounced dead. That night, another storm blew up, filled the tent with snow, and blasted Weathers out of his sleeping bag. He was found lying in the snow the next morning.

Weather’s lower right arm and hand were amputated. He asserts that the life-altering realizations that occurred on the Everest climb were worth the physical cost.

The next morning, Weathers was guided by three other climbers down to 20,000 feet, where he was effectively stuck. He was too ill to get further down the mountain and he was still too high for a helicopter rescue. But then, another miracle happened. A daring Pakistani pilot risked his life for a man from another country and religion – and succeeded.

Weathers ended up losing part of his nose, his right hand and lower arm, part of his left hand and several toes to frostbite, but he survived, and he was there to tell the crowd at the Simmaron event that the ordeal was worth it. The loss of his hands, he said, was a small price to pay for getting back his relationship with his family.

What might a story of survival against all odds on the tallest mountain in the world have to say to people with ME/CFS/FM?

Keeping On Keeping on

Weathers never should have woken up. Then partially blind, hypothermic, etc., by all odds he shouldn’t have made it to camp. He had only a vague idea of where it was. Daylight was quickly running out. His eye problems left him slipping, sliding and falling constantly. He’d lost 30 pounds and was at the end of his rope physiologically. He had no roadmap – no decent expectation that he could survive. He simply knew that in order to have a chance of survival, he had to keep walking.

Just as with Weathers, roadmaps for ME/CFS/FM do not exist. Each person’s journey is unique, full of slips and slides, wrong pathways, muddled ideas, mistakes and occasionally victories. All you can do is to be resolved, in the face of everything, to keep “walking”, to keep being informed, to keep participating. Some people do stumble their way into “camp” (health).

The task, though, is far harder for many ME/CFS/FM patients than for Weathers. Beck got off his mountain but many people with ME/CFS and FM, in pain and bed or homebound, live day in and day out, stuck on their own Everests. Beck’s exploits, as inspiring as they are, pale next to the sheer courage and determination it takes many people with ME/CFS/FM for years or even decades – to keep on keeping on.

Just like Beck, without having any idea how they are going to succeed, they keep putting one foot (so to speak) in front of the other.

There’s just no substitute for keeping on. When Weathers got down to 20,000 feet and his wife was told he was still going to die, his wife kept on. Without knowing how she was going to get Weathers off the tallest mountain in the world, she shared his story with everyone she could think of. She told Beck’s story long enough and well enough until it filtered down to one very brave Pakistani pilot.

Through movies, TED talks, videos, blogs and person-to-person interactions, people with ME/CFS are telling their stories – and moving people. There are “helicopter pilots” out there – brave women and men we don’t know about yet (like Pine of the Pineapple Fund) who will be moved to act. All we need to do is keep sharing.

Keeping on – no matter how high the mountain or how treacherous the climb – is the critical element for success.

Conclusion

Weathers’ story was incredibly inspiring. Like many people with ME/CFS/FM, the medical profession gave up on him, and in fact, signed off on his death warrant. Against all odds, though, Weathers was able to survive.

Weathers’ story indicates miracles do happen at times, that serendipity can strike, that helicopters can appear out of the mist at 20,000 feet. Unforeseen discoveries and assistance (the Pineapple Fund’s $5 million donation to the OMF) can happen. We should never discount the possibilities of miracles happening.

Although Weathers got off his mountain, most of us remain on ours. We have our Everests to deal with. Some of Weathers’ realizations while on the mountain could help make our way easier.

There was the critical need to keep putting one foot in front of the other – to stay in the game, so to speak, and not give up even when all is black. Beck shouldn’t have survived, but miracles – unexpected events – showed up. You never know what the future will bring.

There was the need to take responsibility for the mistakes he’d made in his relationships. Finally, there was realization of how empty striving to be a success was for him.

For people with ME/CFS/FM, we can take our own brand of inspiration from Weathers’ survival and his reevaluation of what kept him going on his mountain.

Simmaron gives special thanks to the donor who made Weathers’ talk possible, and to every one of our donors who make our efforts to help get ME/CFS/FM patients off of their mountains possible.

An entire state goes “ME”. That’s never happened before. Courtney Miller of Simmaron, Emily Taylor of the Solve ME/CFS Initiative, MEAction and the USAWG worked together to enroll the entire Nevada Congressional delegation to put its total support behind increased funding for ME/CFS.

This is notable not just because it’s never been done before, but because for years patients in Northern Nevada sought help from Congressman Amodei and Senator Heller with little success. This is the story of persistence and success. Hopefully we’ll be seeing more of this as the attitude towards chronic fatigue syndrome (ME/CFS) shifts.

Courtney and Bob Miller have been advocating for ME/CFS for many years, but when Emily came up with the rather audacious plan to get the entire state delegation on board, they were energized.

Persistence Works

After the elections in Nevada, Courtney Miller and a group of patients recommitted to taking a sustained approach. Not willing to let the decisions of the past stop them, Courtney met the staff of the Congressman and her Senators after the Women’s March in Washington. At that point Amodei got interested in ways to improve the federal agencies’ response to the disease.

Then in a Spring Town Hall meeting Courtney got up to the microphone and publicly asked Sen. Catherine Cortez Masto for her support. With that Sen. Catherine Cortez Masto’s staff got involved and she joined the effort.

Next during the first Lobby Day in ten years (thanks to SolveME/CFS and MEAction) some patients from Nevada met with Cong. Amodei himself and the Senators. Emily, Sonya, Courtney and others created a draft delegation letter (see attachment). In June Courtney returned to DC and visited the office of every member of the NV delegation. This time the response was enthusiastic; Congressman Amodei agreed to sponsor the letter and set a deadline.

Finally, last week Emily from Solve ME/CFS Initiative and Courtney hit the phones, Anita – the go to person for patients in Incline Village – urged Nevada patients to send emails, and Emily set up a Solve ME/CFS Nevada action alert so that more Nevadans could urge their reps to sign on. (The SMCI has an automated and easy way to contact our reps.) By Friday, the entire Nevada delegation agreed to push Director Collins for more funding.

The State Delegation Game

The game now is to get entire state delegations to sign on. Obviously it’s going to be harder with bigger states (although in conversation Emily mentioned the “big apple”). Besides everything else, getting everyone in a state delegation on board is a great game to play. It sends a powerful message when an entire delegation comes together like that.

I asked Emily what was next.

Next steps are to repeat the process with our strong leads in other states and build up to bigger state delegations. A state delegation letter means a single letter sent from every member of congress (senators and representatives) from that state.

We are truly fortunate to have so many strong advocates leading the charge and dedicated partners coming together with this strategy. I am really excited about this tactic because it effectively leverages the relationships we have built in the past year (particularly in the May ME/CFS Advocacy week actions) and it is a strategy that lends itself to our community’s strengths.

Another key advantage of this approach is the consistent pressure it will apply. State delegation letters take time to organize, so a new state delegation letter every couple of months keeps a constant awareness and pressure to act on ME/CFS. I think this is a good way to avoid the “push-crash” cycle we’ve seen in past advocacy efforts.

As for a comment to add – I’d like to send out a special thanks to Courtney and Bob Miller, Anita Patton, Annette Whittemore, and the many Nevadans who took action to make this campaign a success. This was a long-term, team effort. It’s always toughest to be first! Hopefully, we’ll have many more state delegation letters to come. Emily Taylor – SMCI

Who’s next? Now that Nevada has proven it can be done, who’s next? If you want to your state to be the next to go all “ME” email Emily Taylor at ETaylor@solvecfs.org and let her know.

Most people in their late 60’s probably aren’t running half marathons. Alex Ribaroff had run them twice before, when he turned 50 and 60, and he swore he would never do a half-marathon again. But here he is, at age 67, three months into his training, on the verge of doing just that.

Tom was perfectly healthy until he came down with infectious mononucleosis at age 16

This time he’s not doing it to celebrate a milestone. He’s doing it to for his son, Tom. Tom was a strapping young man – athletic, academically inclined and outgoing – when he fell prey at 16 to an Epstein-Barr virus (EBV) infection in the UK. Getting exposed to EBV as a child is usually a piece of cake but if you encounter it as an adolescent, it’s another deal indeed; it’s a very common trigger for ME/CFS.

Tom got hit so hard he had to leave school. Two months later, still not well but itching to get back, he returned – only to get hit harder by another bout. That was five years ago. Tom is at University now, he’s hanging on but everything other than academics – sports, exercise, socializing – is out. It’s no way for a young man to get through college.

Tom and his family went through the same experience that so many other sufferers from ME/CFS have – the fruitless search for help – the suggestions to use CBT and graded exercise.

Slowly, Alex and his wife Denise learned more about ME/CFS, the many people affected, the few experts, its marginalization and it’s need for funding. They’ve come to grips with the fact that their young son has a debilitating and chronic illness that many have not recovered from – and they decided to try and do something about it.

They’re raising money to support ME/CFS research. It’s not like they’re experts at this. In fact, they’re complete novices, but their burning commitment to help is pushing them to do things they’ve never done before.

When I asked them why they were stepping out like this, Alex and his wife described the helpless feeling they had watching their young son get sicker and sicker. “You expect your children to be healthy” he said, and if they’re not then “you expect the medical profession to be able to do something about it.” No one should have to experience that feeling around their children.

By chance, a year ago, a friend of the family sent them an article from the Guardian newspaper in the U.K., talking about the research advances being made by Mady Hornig and the Center for Infection and Immunity.

Hornig MD, and Ian Lipkin, a world-renowned pathologist, have taken a special interest in ME/CFS. The blood and spinal fluid studies they’ve done in collaboration with the Simmaron Research Foundation (SRF) and other groups found that ME/CFS patients first exhibit a pattern of high immune activation which is followed by immune exhaustion. Their joint CII/Simmaron Research Foundation cerebral spinal fluid study found a degree of immune dysregulation similar to that found in multiple sclerosis. (An expanded study is underway). Another joint CII/Simmaron Research Foundation study identified a new class of ME/CFS patients (“atypical patients”) who have unusual disease trajectories and test results). Their latest study found dramatic differences in the gut flora which may eventually lead to targeted gut therapies.

A conversation with Hornig led the Ribaroff’s to get in touch with Dr. Peterson and the Simmaron Research Foundation. Only then did they feel that they had found a clinician who understood this illness and might be able to help them.

When they found out how many people’s lives are blighted by the disease, and how many people’s future has been darkened by the cloud of ME/CFS hanging over them, their focus shifted. The fight became about more than for Tom. It became a fight for everyone who has this illness.

So, Alex at age 67 is now lacing up his running shoes for a half-marathon he didn’t ever expect to run again. He’s raising money for two groups – the Simmaron Research Foundation and Columbia University’s Center For Infection and Immunity- that provided them with answers when they desperately needed them.

Alex was appalled by the helpless feeling he and wife had when Tom got sick. Now they’re doing something about that.

They’ve put the call for help far and wide to their friends, many of whom were shocked to hear the healthy, young man they’d known was struggling so much. Jen Brea’s moving “TED talk” – now seen by over 1,200,000 people – proved to be a powerful introduction to a disorder many of them had never heard of. Alex and Denise hope to raise $75,000 – the first $25,000 of which they will match.

The Ribaroffs are getting more involved. They’re going to meet with Dr. Peterson, Dr. Hornig and other luminaries at the London “Invest in ME” conference, to better educate themselves about global advances in research.

But first comes the run. In just two days Alex will put the memories of the last two runs aside and step out onto the track and run – for his son and everyone else with ME/CFS.

Please support Alex and Denise‘s commitment to help their son and many others with your donation to the Simmaron Research Foundation here. (The Simmaron Research Foundation will receive half of the donations raised and will provide the other half to support Ian Lipkin and Mady Hornig in their ME/CFS work at the Center for Infection and Immunity.) PayPal and Credit Cards accepted.

Update: Sixty-seven year old Alex Ribaroff successfully completed the Bermuda Half-Marathon on the 25th of May 🙂

Below are Simmaron Research’s real time tweets from the FDA Drug Development Workshop on April 25th and April 26th last week. They are notes from most of the workshop sessions. While tweets usually have the most recent on top we have swapped this so the tweets here are in chronological order so you can follow the conversation from the beginning. If you are interested in more updates from Simmaron’s Twitter page you can follow us here @RedefiningMECFS.

The FDA released its background report and its list of committee members and, if you want to compare the two, the Agency was even-handed; the report was highly critical and the committee members they picked boded well for Ampligen chances..

REPORT

Harshly Critical Analysis

We knew FDA Advisory Meetings can be intense, rough environments. With the FDA background report on Ampligen you can count that as confirmed. This is not going to be easy for Hemispherx..

The FDA analysis of the Ampligen trials, focusing on methodological issues, mistakes and what it believes are inadequate efficacy and safety data does not, on the face of it, appear to bode well for Ampligen and the market agreed with the stock shaving off half its value the day the report was released.

FDA reports do tend to highlight negatives, not positives which makes sense given the way the meetings are set up; the sponsoring drug company presents its data in its best light, then the FDA does its best to poke holes in it, and then the independent review committee decides.

In the meantime be prepared for a difficult hearing. These FDA Advisory hearings have been described as ‘blood baths’ from which few companies and drugs escape unscathed.

Background

A harsh FDA report presented two days before the meeting did not bode well for Ampligen

The long and rather tattered history of Ampligen at the FDA since 1988 is outlined. The first interagency transfer to a new department occurred in 1992. The long gap between the first proof of concept trial (1990-1991) and the confirmatory trial (1998-2004) probably demonstrated how difficult it was for Hemispherx to raise the money needed to carry out the second trial.

Ampligen’s New Drug Application (NDA) submitted on Oct, 2007 was refused filing because it was missing study reports, ECG and laboratory data, case report forms, ‘dose ranging’, ‘inconsistent statistical plans’, clinical pharmacology data, carcinogenicity data andhad database discrepancies. This was a long list but Hemispherx fixed some of the problems and explained others, and in the first third of 2008 quickly resubmitted the application and it was allowed to move forward.

“Your two main studies (AMP-502 and AMP-516) do not provide adequate evidence of effectiveness or safety.”

In 2012, after being moved to another branch of the FDA, Hemispherx requested to be allowed to re-analyze the data from the second, larger, confirmatory trial. The agency was leery about this approach stating “It would be unusual for this type of data to provide adequate evidence of efficacy.” but allowed the process to continue forward stating the efficacy issues would be addressed at the final review..

Two Trials

The FDA will be relying on evidence from two trials; AMP-502 and AMP-516. (The agency is, unfortunately, not using confirmatory data generated from patients who continued on the drug after the trial because that data was not placebo-controlled.)

Problems had occurred. After finding that the original exercise protocol was too difficult, however, Hemispherx changed the protocol and eliminated the first seven patients from the analysis. ( If those patients are included in the analysis the significantly positive effects disappeared. )

The trial was originally supposed to last for a year but after an interim analysis it was stopped after 24 weeks. The FDA drew attention to the fact that the statistical analysis plan was written and dated 16 years after the completion of the study and later noted ‘multiple protocol violations’ including patients restarting their other medications during the trial had occurred.

Second Trial (1998-2004) – The second larger trial (516), designed to confirm the first trial’s results, failed to show significant increases in self-reported functioning or ETT. Recently Hemispherx re-analyzed the data using patients with lower disease duration (1-10 years) and dichotomous branching techniques and received significantly positive ETT results but still no significant changes in self-reported functionality, daily living, SF-36 or symptom scores.

Hemispherx found that the percent of patients reaching 25% and 50% increases from baseline was significantly increased in patients receiving Ampligen and that patients with lower duration illness (<10 years) were more likely to benefit. Despite reports in the literature that lower duration patients (< 2 years) do tend to respond better the FDA found ‘no scientific rationale’ for the lower duration analysis and advised caution in interpreting them.

Several issues were reported including using median KPS values for some patients and minimum median values for others. Hemispherx also chose to use any response (ie the best response recorded) during the duration of the trial for its endpoint instead of set responses at the end of the trial.

The re-analysis was helpful but the FDA questioned whether these types of re-analyses are suitable for determining efficacy suggesting they are better suited for ‘hypothesis testing’.

Due to the nature of analyses conducted after data unblinding, the Agency generally considers post-hoc analyses to be hypothesis generating rather than forming the primary basis of efficacy for an application.

Hemispherx was caught in the first study with an exercise protocol that was apparently wiping the participants out. In the second , larger ‘confirmatory’ study Hemispherx had to analyze the results differently to get positive results in the exercise testing but not significantly positive results in self-report tests. Changes in protocols and analysis are often red flags to reviewers and questions were raised why a protocol and analysis would work in one trial and not the other.

It was rough stuff but a Hemispherx rep appeared unflustered and confident that the company was ready to respond to the FDA’s report.

Tough Subject – With its subsets and its vague definition, ME/CFS is a difficult field to test any drug in, and drugs that practitioners say have positive results in some patients have failed to achieve them in placebo-controlled trials. If the disorder is larded with subsets then the results of any major trial of a drug that works probably should appear like Hemispherx’s did; that is, it should have weakly significant results because of the patients in the trial who have a different type of disorder altogether. We should also know of people who had excellent results (we do) and doctors who prescribe the medication to targeted patients should have good results (they do).

Subsets will inevitably complicate matters in any clinical trial for chronic fatigue syndrome (ME/CFS) as its defined now

The FDA must realize that it’s facing an unusual challenge in a disorder that is so poorly defined. The background report did not take into account the possibility of subsets watering down the study results but the Committee is made of several members who are well aware of this problem. Dr. Unger of the CDC, for instance, has publicly stated she is sure this is true and is engaged in a study that should help ferret them out.

Indeed a recent analysis suggested the subset problem meant Hemispherx started its trial with one of its hands tied behind its back. Throw in the fact that it’s a small company with limited resources and you probably get what we see; midstream changes that attempt to account for new information and re-analyses to target possible subgroups.

Ampligen’s trials had no way to account for this meta-population problem beyond looking for interesting trends within the data set. And that is what they did… No one seems to know what an appropriate biomarker for the general CFS population is, but the FDA is holding Ampligen up to an unrealistic standard nonetheless. In the end, HEB did find statistical support that Ampligen provides a biologically meaningful impact on the lives of at least some patients with CFS.

The problems facing Ampligen-or any putative therapy for CFS for that matter, is that the underlying cause(s) are unknown. As a result, there are quite possibly distinct sub-groups within any potential CFS study population with markedly distinct pathophysiologies, and hence

Safety

Hemispherx has reported that tens of thousands of doses of Ampligen have been given without issue but the FDA will rely on the results from ‘only’ 567 patients of which ‘controlled data’ are available for only 162. The FDA stated that for drugs intended for long-term treatment they would like at least 1,500 people exposed to the drug for short term periods and 100 for over a year.

Here, too, the FDA cited numerous issues including serious adverse events not reported, marked laboratory abnormalities not reported, miscoding of adverse events and reasons for patient discontinuation of the trial and incomplete/misleading data presentation. Some serious adverse events that resulted in hospitalization were not reported. The discrepancies were enough for the FDA to call into question the data from all the trials.

On the other hand, the side effects that showed up more in patients receiving Ampligen (flu-like symptom, chills, vasodilatation, shortness of breath ) were not particularly significant. Other more serious side effects did occur but not more significantly in patients receiving Ampligen but the Agency expressed concerns about them.

Overall, the Agency has concerns regarding the reliability of the safety database for Ampligen, based upon lack of appropriate documentation and reporting. While review of the safety database for Ampligen suggests that the drug induces a systemic inflammatory reaction with a number of serious events of concern, the lack of reliable reporting prevents any accurate assessment of frequency. The key safety issue for discussion at the advisory committee meeting is whether conclusions can be drawn from the data as it stands …

Hemispherx will explain why the safety data is sufficient and why oversights, omissions, etc. occurred and why they shouldn’t bear negatively on the review.

COMMITTEE MAKEUP – the Good News

Taking the committee makeup into account one analyst predicted a close but positive vote. At least six people have history with chronic fatigue syndrome and I would be very surprised if Komaroff, Marshall weren’t strong yes votes and the others strongly leaning towards yes. If those six vote yes they’re two votes away from a tie vote and three from a majority vote. For me, I think Marshall can be very persuasive once he gets going J.

The harsh FDA report was produced by statisticians with little knowledge of the disorder but the FDA also produced a committee with a core of members with extensive knowledge of ME/CFS. The Committee vote is the key. Will Hemispherx and the patient advocates be able to convince the committee members to overlook a harsh FDA report? We’ll see.

The vote will come at the end of the day. The committee members will be asked to vote all at once so that the members are not influenced by the others votes.

The FDA will take everything into account and release its decision on Feb 2nd. They could approve the drug outright (not likely to happen), approve it with conditions, ask for more studies or just slam the door on the drug.

Decades of hope and work for Ampligen, still the only drug ever produced for CFS, will culminate on Dec 20th.

by Cort Johnson

Ampligen’s time is finally here. Twenty years of effort and hope will culminate on the early evening of Dec 20th, when, following an all-day hearing, an FDA Advisory committee will determine Ampligen’s fate. Palms will be sweating and hearts will be pounding that evening as patients, physicians and their supporters and researchers with decades of work on the line await what will be a momentous decision.

Produced by Hemispherx Biopharma, Ampligen is and has been the only drug under development for chronic fatigue syndrome for over twenty years. No other drugs are waiting in the wings and no other companies appear interested in putting years of effort and millions of dollars into producing or even testing a drug for this disorder.

It’ll all come down to 6-10 or so independent ‘experts’ opinions on whether this drug is safe, effective and worth putting on the market.

Prior to the big decision we’ll see presentations from Hemispherx, the FDA and ME/CFS patients. Dr. Bateman, Dr. Snell and Hemipherx representatives will present for Ampligen.

LOCATION: Open to the Public

Anybody can come and we hope as many people as possible come and if they wish, give testimony. Patient Testimony will be given in 3-minute slots from approximate 1pm to 2:30

Hemispherx is likely to face tough questioning at the FDA Advisory Committee meeting for Ampligen

TOUGH ENVIRONMENT

According to someone who’s been there, FDA Advisory Hearings tend to be in-your-face type affairs in which tough questions and a critical attitude are the norm. If Hemispherx is getting whacked around at the hearing don’t attach too much significance to it; every pharmaceutical company gets hammered at these hearings – even those that get their drugs approved.

My understanding is that there will be two presentations; the FDA will present its interpretation of the data and Hermispherx with Dr. Bateman, Dr. Snell and its own raft of professionals will present its case. The FDA Advisory Board, made up mostly of rheumatologists will pepper each group with questions and come to a decision on three questions.

Does Ampligen work ( efficacy)?

Is Ampligen safe?

Do Ampligen’s benefits outweigh its risks?

Each member will answer each of these questions live and we’ll get their decision in public that day. From there the FDA will take their reports into account and submit their final ruling on Feb 3rd, 2013. They almost always follow the decisions of the Advisory Board.

Still Some Unknowns

There’s still quite a bit about this meeting that we don’t know and that the FDA probably won’t share until 2 days before the meeting. Take no offense at this – this, for some reason, is standard FDA procedure. (The FDA states they will provide the information at least two day before the meeting, which everybody is taking to mean it will happen two days prior. )

At Least Two Days Before the Meeting..We Will Know

Panel Makeup – The final makeup of the panel. We do know that the panel will be made up of persons from the Arthritis Advisory Committee and perhaps others but we’re not sure who. The FDA website states the committee is made up of 12 slots, six of which are vacant (including the Chair ). Of the six persons listed on the website one of them, Dr. Irwin Russell, is director of the Fibromyalgia Research and Consulting Clinical Research Section of South Texas. Another is an immunologist; none of the others, at first glance, have any indirect connections with CFS or FM.

Patient Advocate – the identity of the ‘Patient Advocate’, who presents the needs of the patient community to the panel will be listed.

Discussion Points/Questions – Hemispherx will want to rest up beforehand because the FDA may list a series of questions they want information on just two days before the epochal hearing takes place. Hemispherx may be cramming all the way up to the hearing..

Webcast Link – We’ll get the link for the webcast.

The information will be available here or maybe here; it’s not entirely clear from the notice..

STAR ALIGNING?

Ampligen has been under review of one sort or the other since the nineties, but after a surprisingly good year for Ampligen there is good reason to hope for a successful outcome. In July the FDA reversed a devastating 2009 decision requiring Hemispherx to produce new expensive studies which appeared to put Ampligen out of reach for good. With chronic fatigue syndrome gaining more prominence, though, and with the FDA being given a new mandate to give serious, underserved illnesses a foot up, Ampligen was back in the mix in 2012.

Key Legislation Provides An Opening

The 2012 FDA Safety and Innovation Act (FDASIA) passed in July appears to have played a key role in reversing Ampligen’s fate. The FDASIA encouraged the FDA to use a process called ‘accelerated approval’ which allows the Agency to conditionally approve drugs for ‘serious and life-threatening illnesses’ while drug companies worked on proving efficacy. This is a perfect mechanism for small drug companies like Hemispherx which would be allowed to market the drug and use the profits to fund further studies it couldn’t otherwise undertake.

Have the pieces come together for Ampligen and Hemispherx?

Coming just two days after the passage of FDASIA, the FDA turnaround on Ampligen might indicate the FDA is using the drug to make a statement regarding its willingness to follow FDASIA guidelines. Indeed, Sue Sutter, a noted business/pharmaceutical journalist suggested the FDA’s change of direction on Ampligen may have been directly influenced by the FDASIA.

More groundwork was laid on Sept 13th when FDA Deputy Director, Sandra Kweder, M.D. publicly stated on an ME/CFS Teleconference that the FDA considers ME/CFS to be a “serious and life threatening disorder”. An FDA notice for the meeting that specifically mentioned ‘accelerated approval’ and ‘unmet medical needs’ with regard to drugs for ME/CFS indicated that the FDA, again, was specifically drawing attention to FDASIA guidelines.

The FDA’s decision to hold an ME/CFS advocacy teleconference and use ME/CFS to produce it’s first Stakeholders Meeting for a disorder in decades next year also suggests a positive stance by the FDA. (One FDASIA provision calls for more patient involvement.) Sue Sutter called these efforts “a major step in the FDA’s efforts to raise the profile of CFS as a drug development target”.

Finally a Jan 2011 decision to consolidate, after being bumped around to six divisions, oversight of CFS treatments in the Division of Pulmonary, Allergy and Rheumatology Products, suggested the Agency was trying, finally, to get its arms around this disease and its challenges.

THE PLUS’S

The Drug

Ampligen out-performed a placebo in exercise trials

Patients on the drug were able to reduce their use of other medications, some of which can be harmful

Over 1,000 patients have been administered over 90,000 doses of the drug safely

Even long term use of Ampligen appears to be safe (ie does not cause disease)

Chronic fatigue syndrome is a relatively common disorder with no FDA approved drugs (and no other drugs in sight) which presents high economic costs to people who have it and to the nation as a whole

CDC figures suggest that chronic fatigue syndrome is functionally as disabling as multiple sclerosis and 10 times as common

Other disorders with few FDA approved drugs have been given more latitude with regard to drug efficacy at the FDA; ie if no other treatments are available the FDA is willing to relax its efficacy requirements.

FDASIA passage supports accelerated approval in cases where serious unmet needs are present and the drug is safe.

The MINUSES

The biggest hurdle Hemispherx has to deal with is the age and number of its studies. In 2009 the FDA wanted a brand spanking new study with lots of bells and whistles. The FDA relinquished that stance earlier this year but Hemispherx could be penalized for not being a billion dollar pharmaceutical company with resources to burn. Hemispherx’s re-analysis of its original data had Ampligen performing better. Will that be good enough?

Controversial Disease – with a poor definition. Will the disorders negatives trump its positives and the community’s needs? No federal agency has ever made the CFS communities needs a priority. Will the FDA be the first?

DECISION TIME

Taking Responsibility – The FDA rarely does not follow the decisions of its independent reviewers but the responsibility for the final decision is theirs. They, of course, contributed to Hemispherx’s dilemma by moving the drug around to six regulatory teams. Frustrated with these kind of bureaucratic bottlenecks and the slow pace of drug approvals, Congress acted in 2012 to make the FDA work more effectively for chronically ill people in the U.S.

It’s hard to see what the FDA has to lose by giving Ampligen Accelerated Approval status. They know the disorder is serious, they realize the community has huge unmet needs, they have proof of efficacy and most of all, they know the drug is safe.

POTENTIAL GAME CHANGER

Ampligen approval would change how ME/CFS is viewed leading to more respect and more funding

If approval occurs patients will get access to a drug that’s worked well for many, doctors will view ME/CFS as more of a treatable disorder and immune research will heat up. Future studies examining Ampligen’s effects could very well pave the way for a biomarker and uncover subsets.

FDA approval would also give pharmaceutical companies the message the FDA is serious about finding ways to get drugs to this community and that it will work with them where it can to do. A thumbs down could suggest the opposite.

Maybe the biggest change, though, would be a change in context for ME’/CFS. If you can change the context in which a thing occurs opportunities that were denied to it come naturally. An FDA approval would make this disorder more real as a disorder thus giving it more access to the opportunities other ‘real’ disorders have. The FDA does not approve drugs for figments of the imagination; it approves drugs for HIV, pneumonia and cancer. Ampligen approval would begin to thrust chronic fatigue syndrome into that realm and disorders like that get respect, they get interest and they get funding.